This is a Major Research Program responding to the announcement in the NIH Guide, Vol. 5, No. 8, June 25, 1976, National Institute of Child Health and Human Developmental Request for Application. The overall goal of this Major Research Program is to understand the dynamics and control of oxygen delivery to the fetus in utero. The program encompasses investigations at several hierarchical levels; cellular, organ, system, and integrative studies involving the entire organism. The integrative and environmental studies will explore dose-response relations and critical levels of hypoxic hypoxia and carbon monoxide hypoxia, and their effects of fetal growth, and placental diffusing capacity; will examine the relation of fetal oxygenation to placental insufficiency, and will study adaptive mechanisms to high altitude acclimatization. It also will examine the effects of maternal exercise on fetal growth, uterine blood flow, and placental diffusing capacity, and the mechanisms which produce changes in these functions. We also shall develop a mathematical model of the overall fetal oxygen delivery system. We will seek to understand the role of factors which control fetal cardiac output such as: mean systemic pressure, baroreceptors, and chemoreceptors; and the factors which control peripheral blood flow such as: carbon dioxide, hydrogen ion, osmolality, catecholamines, etc. A major portion of the proposal concerns the control of fetal fluid volumes, blood volumes, and interstitial fluid volume, and the role of the four Starling forces. This study includes examinations of the roles of hormones such as: vasopressin, renin-angiotensin, cortisol, and prolactin on fetal and amniotic fluid volumes. We also will study problems relating to organ oxygenation and its relation to metabolism. We will explore the control of blood flow to specific regions of the developing brain, and its relation to electroencephalographic activity and metabolism; and the control of blood flow to the liver. Finally, we will institute a series of studies of the control of cellular respiration, and the mechanism of oxygen chemoreception in the fetus and newborn.